Recommended Adjuvant Therapies for Stage 4 Breast Cancer
For stage 4 breast cancer, adjuvant therapy should be tailored based on receptor status, with endocrine therapy plus targeted agents for hormone receptor-positive disease, anti-HER2 therapy for HER2-positive disease, and chemotherapy for triple-negative or rapidly progressing disease. 1
Treatment Based on Receptor Status
Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer
- Endocrine therapy alone or in combination with targeted agents is the preferred initial approach for HR-positive, HER2-negative metastatic breast cancer 1
- Aromatase inhibitors in combination with CDK4/6 inhibitors have demonstrated improved progression-free survival compared to AI alone and should be considered as first-line therapy 1
- Premenopausal women should receive ovarian suppression/ablation and then be treated similarly to postmenopausal women 1
- Second-line options for patients who progress on or within 12 months of completing adjuvant endocrine therapy include:
- Fulvestrant with a CDK4/6 inhibitor
- Fulvestrant with alpelisib for tumors with PIK3CA mutations
- Everolimus combined with an AI, tamoxifen, or fulvestrant
- Monotherapy with fulvestrant, aromatase inhibitors, or selective estrogen receptor modulators 1
HER2-Positive Metastatic Breast Cancer
- For HER2-positive, HR-positive disease: HER2-targeted therapy plus chemotherapy or endocrine therapy in combination with HER2-targeted therapy 1
- Adding trastuzumab or lapatinib to an AI has demonstrated progression-free survival advantage compared with AI alone 1
- For HER2-positive, HR-negative disease: HER2-targeted therapy in combination with chemotherapy is the standard approach 1
Triple-Negative Breast Cancer
- Chemotherapy remains the primary systemic treatment option for triple-negative breast cancer, with anthracycline and taxane-based regimens recommended as initial treatment 1
Chemotherapy Options
Docetaxel
- For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose is 60-100 mg/m² administered intravenously over 1 hour every 3 weeks 2
- Toxicities may warrant dosage adjustments and administration should occur in a facility equipped to manage possible complications such as anaphylaxis 2
Paclitaxel
- For metastatic breast cancer after failure of initial chemotherapy or relapse within 6 months of adjuvant chemotherapy, the recommended dose is 175 mg/m² administered intravenously over 3 hours every 3 weeks 3
- Premedication with dexamethasone, diphenhydramine, and cimetidine or ranitidine is required to prevent severe hypersensitivity reactions 3
Bone-Targeted Therapy
- For patients with bone metastases, bisphosphonates or denosumab should be added to systemic therapy 1
- Recommended agents include pamidronate and zoledronic acid, with denosumab shown to significantly delay time to first skeletal-related event compared to zoledronic acid 1
Monitoring and Treatment Adjustment
- Patients should be monitored every 2-3 months during endocrine therapy or after 2-3 cycles of chemotherapy 1
- Upon disease progression, patients should be switched to the next line of therapy 1
Special Considerations and Caveats
Treatment Approach
- A combined treatment modality based on a multidisciplinary approach is strongly indicated for advanced breast cancer 1
- The goal of treatment for stage 4 breast cancer is to improve length and quality of life, as this stage is considered treatable but not curable 4
Endocrine Therapy Considerations
- Letrozole has shown efficacy in the treatment of postmenopausal women with advanced, hormone-sensitive breast cancer 5
- In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment with significantly longer time to disease progression (9.4 vs 6.0 months) 5
- Common adverse events with endocrine therapy include hot flushes, arthralgia, myalgia, and arthritis 5
- Long-term effects on bone mineral density and lipid profile may require monitoring 5
Treatment Sequencing
- Systemic therapies for metastatic breast cancer include endocrine therapy with targeted agents (CDK4/6 inhibitors, PI3K inhibitors) for hormone receptor-positive disease, anti-HER2 therapy for HER2-positive disease, PARP inhibitors for BRCA1/2 mutation carriers, and immunotherapy for some triple-negative disease 6